System for delivery and monitoring of administration of controlled substances

ABSTRACT

A system is provided for delivery and monitoring the administration of controlled substances which includes one or more databases including a national database of controlled substance users, a database including physician/pharmacy information, a controlled substance delivery device and a docking station for use together with a network and software for communication between the various components of the system.

FIELD OF THE INVENTION

The present invention relates to systems for administration andmonitoring of controlled substances, which includes an informationnetwork, a national database of controlled substance users, one or moreadditional databases, and a drug delivery device. The system provides avariety of mechanisms for monitoring the administration and use ofcontrolled substances with the ability to adjust administrationparameters based on input from qualified medical personnel.

BACKGROUND OF THE TECHNOLOGY

Currently, delivery and tracking of the administration of controlledsubstances in both the in-patient and out-patient setting have clearlimitations with regard to both safety and the potential for abuse.

Controlled drug delivery technology represents an area of activeresearch and controlled drug delivery systems offer numerous advantagesas compared to conventional dosage forms, which include improvedefficacy, reduced toxicity, improved patient compliance and convenience,as well as minimizing the potential for abuse.

U.S. Patent Publication No. 20060031099 discloses methods for theadministration of pharmaceutical compositions using inkjet-based drugdelivery devices and a healthcare system that provides for transfer ofinformation from one or more healthcare nodes of the system to a “smartdevice”. The system enables real-time synchronization of data andrecords with the drug-delivery device and other healthcare nodes, suchas medical professionals, computer systems, fluid reservoirs, or medicaldevices, such that computer systems within the healthcare system have upto date information for generating instructions for the administrationof a drug, making decisions regarding the health of a patient, andcreating a health history for the patient for later analysis.

U.S. Patent Publication No. 20060026035 discloses a computer aidedinteractive medical management information and control system andmethods including one or more devices and a computing platform andassociated software that assists a health care provider in performingtreatment on a patient.

U.S. Pat. No. 6,914,668 discloses a personal identification and securitysystem including a personal identification verification system (such asa biometric information comparison system), a controlled substancedetection and identification system (such as a spectroscopic detectionand identification system) and an alarm indicator.

U.S. Pat. No. 6,762,684 discloses a processor implemented monitoringsystem which includes a sensor coupled to the processor for sampling aphysiological parameter of a subject such as a unique identificationparameter of a subject heart function, e.g. blood pressure, pulse, bloodoxygen level, as well as unique subject, i.e., identifying physiologicalparameters such as DNA characteristics obtained from sampling of bloodor other fluids such as saliva, perspiration, etc., a retinal scan, afingerprint scan, voice recognition and the like, coupled with alocation ascertaining system, e.g. a GPS system. The mobile unit iscoupled via radio, cellular telephone or other wireless or wiredcommunications link with a central station and can transmit informationpertaining to the condition as well as the location of the subject.

U.S. Patent Publication No. 20050049464 discloses a wirelesscommunication system that includes a remote pharmaceuticaladministration device for monitoring the vital signs of a patient, ananalysis processor for receiving the vital signs, a transceiver fortransmitting the vital signs over a wireless network and receiving anaction plan over the network, and an administration means foradministering a prescribed medication to the patient.

U.S. Patent Publication No. 20050054942 discloses systems and methodsfor monitoring therapeutic drug concentration in the blood by detectingmarkers, upon exhalation by a patient after the drug is taken, usingelectronic sensor technology and a reporting system.

U.S. Pat. No. 6,824,512 (Medtronic, Inc.) discloses a closed loop systemfor monitoring drug dose, intake and effectiveness which includes a pilldispenser in communication with at least one implantable medical device.The system includes high speed computers and databases relating topatient history and device information.

U.S. Pat. No. 6,190,326 discloses a system for collecting patientrespiratory information which includes a base unit and a removablemouthpiece.

U.S. Pat. No. 6,039,251 discloses a method and system for controlling anin-home medical device, such as a drug delivery pump, wherein a controlprogram or “prescription” for control of the device is encoded on aportable card. Data relating to the device can be saved to the card, anda security program is provided which ensures that only authorizedpatients can use the medical device. Remote access to the medical deviceis provided through a communication system between the controller forthe medical device and a remotely located computer.

U.S. Pat. No. 5,752,620 discloses a pill dispenser, comprising acontainer constructed to hold a plurality of pills, with a pill releasemechanism provided to dislodge the pill from the pill holder bypneumatic pressure and sensors located on the exit port to detect thepresence of a dispensed pill, which is recorded by an attached computer.Optionally, a locking device is attached to the pill dispensing unit toprevent unauthorized dispensation of medication.

U.S. Pat. No. 5,710,551 discloses a system for the remote monitoring ofin-home self-medication to assure compliance with prescribed dosageschedules.

U.S. Pat. No. 5,945,651 discloses a medication dispensing systemincluding a relatively small, microprocessor-controlled machine thatassists in the accurate execution of a physician-prescribed medicationregimen. The machine can be used as a stand-alone unit, or can beintegrated into a centrally-controlled pharmaceutical network.

U.S. Pat. No. 5,995,938 discloses a medication compliance system havingan output device and a computer in communication with the output devicefor use in printing a label.

The related art does not disclose or suggest systems for delivery andmonitoring of the administration of controlled substances. Although anumber of references mention the concept of computer monitoring orcontrol of drug delivery, for example, an “electronic pill box” and thelike, the current invention provides a number of features not taught orsuggested by systems currently known in the art.

Also not found in the relevant art is a drug delivery device (that doesnot require the opening and closing of a lid or other hinged aperture)for drug delivery dosage forms, wherein the device includes the featuresthat contribute to the current invention, namely, a drug reservoir, alock out feature and a means of communication with a computer network,i.e. via a docking system.

There is a need for a drug delivery system that provides for improvedsafety and efficacy while eliminating or minimizing potential for abuseincluding for example: a security feature that prevents unauthorizedaccess to stored drug, a lock-out feature, a dose counting feature, amemory means for retaining information about dose delivery, and aninterface for exchanging information with another device such as acomputer/information network.

There is therefore, substantial interest in the development of systemsfor drug delivery, more specifically administration of controlledsubstances, in both the hospital and out-patient setting.

SUMMARY OF THE INVENTION

The invention provides computer aided systems and methods for deliveryand monitoring of controlled substances. The systems include a drugdelivery device. Information from the drug delivery device can becommunicated via a computer network to one or more databases. The drugdelivery device may communicate by way of a docking station, wherein thedocking station provides a connection to a computer network andinformation is transmitted bidirectionally between the drug deliverydevice and a computer network, for example, a wireless computer network.

More specifically, the systems include: (a) an information networkcomprising a computing platform and software comprising a searchmechanism running on the computing platform; (b) at least oneinformation storage device connectable to the computing platform forstoring the software; (c) one or more databases for storing patientusage information and prescription information for at least onecontrolled substance; (d) at least one device for administering acontrolled substance to a patient connectable to the information networkfor transmission of patient usage information to the informationnetwork; and (e) a communications interface for establishing abidirectional communication link to at least one external source.

The prescription information includes information regarding the patientand is stored in a national database of controlled substance users. Thenational database of controlled substance users is in compliance withthe Health Insurance Portability and Accountability Act (HIPAA)regulations and provides coded or encrypted patient information to avoidmisuse of information or inappropriate access.

In using the system, prescription information for at least onecontrolled substance is entered into the information network by aregistered user.

The system provides for a search of the national database and a softwaregenerated alert when a search of the national database indicates thatprescription information for more than one controlled substance has beenentered into the national database for the same patient during the sametime period or when a search of the national database indicates thepossibility of a drug-drug interaction. The system provides a means forthe alert to be transmitted to the prescribing physician and registereduser who entered the information by way of an email, a text message, apage, a phone call or other communication.

The system also provides a means for a drug delivery device foradministering the controlled substance to a patient to be connected tothe information network by way of a docking station using a connectionselected from the group consisting of a computer (i.e., a USB port), aremovable card (or other media), a phone line, or a wireless connection.When docking occurs, patient usage information is transmitted to theinformation network and stored in at least one database.

The system further provides for collection of information on biologicalparameters of the patient using a docking station. The information onbiological parameters of the patient may include pain score, anxietyscore, insomnia score, temperature, pulse, blood pressure, respiratoryrate, oxygen saturation, blood chemistry and bodily fluid chemistryinformation.

The device for administering a controlled substance typically includes adetection mechanism for patient identification such as an RFID tag, apassword, a pass code, fingerprint information, optical information,voice recognition, facial recognition or the results from DNA analysisof a bodily fluid sample.

Verification of patient identification may be required on a daily,monthly or other basis, in order for the device to remain activated. Thefrequency at which verification is required determined and may beadjusted by the prescribing physician.

The system may further include at least one input device for manualentry of information into the system by a registered user by way of amicrophone, a touch screen, a keyboard, or a graphical input device.

The system provides for manual entry of prescription information andchanges in prescription information. Such manual entry may occur inresponse to an alert or for other reasons.

Information may be transmitted to, from and within the system by way ofa telephone, an Internet connection, a WAN network connection, a LANnetwork connection, a wireless connection or a satellite connection.

In using the system, a controlled substance is loaded into a device foradministering a controlled substance and dispensed to a patient when noalert is generated by the system and the device is initially activatedfollowing verification of patient identity.

The patient may self-administer the controlled substance when the devicefor administering a controlled substance is in an activated state.

DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic depiction of the functional elements of thecontrolled substance delivery and monitoring system of the invention,which include a registered user and/or prescribing physician, alsotermed “qualified medical personnel” [1], who has received training inuse of the system by the office of the prescribing physician and whoenters the prescription (Rx) information into the computer systems suchthat it is transmitted to a national database of controlled substanceusers [2] containing an index of users and Rx information; the systemthen provides a double check for other prescriptions and the identity ofthe patient. When a patient brings a prescription for a controlledsubstance to a pharmacy, the pharmacist [3] double checks the Rxinformation and initial patient information in the system The initialpatient information is stored in a national database of controlledsubstance users, which is automatically searched for accuracy and otherparameters when a patient brings a prescription to a pharmacy to befilled. The system software checks for other controlled substanceprescriptions for the same patient and for drug-drug interactions. Ifthe prescription information is accurate and no drug-drug interactiondetected, a controlled substance delivery device [4] is filled with theprescribed medication, is dispensed, then docked with a docking station[5], and information is bidirectionally transmitted between theinformation network and the device via the docking station. In mostcases, then the patient identity is verified and the controlledsubstance delivery device is unlocked (activated) [6] and ready for use.Alternatively, if a problem is detected with the prescriptioninformation or a drug-drug interaction detected, an alert is initiatedand sent via the information network to a physician database [7], theregistered user who input the prescription information and theprescribing physician. The activated delivery device [6] is used todeliver medication to the patient [8] in a controlled manner. Both thenational database of controlled substance users and physician databaseare part of an information network which receives and sends informationto the controlled substance delivery device by way of a docking station.In addition, information may be transmitted bidirectionally between theinformation network to the patient's chart [9]. A* indicates a stepwhere an alert may be generated. Typically, the docking station is at aphysician's office, a pharmacy and/or the patient's home.

DETAILED DESCRIPTION OF THE INVENTION

The following disclosure describes the systems and methods whichconstitute the invention. A detailed disclosure of the systems andmethods of the invention for the delivery of controlled substances isprovided herein.

The controlled substance delivery and monitoring system of the inventionis not limited to specific controlled substances, formulations, dosagesforms, delivery devices, or methods of use. As such, the systems andmethodology for treatment of the medical condition of the patientdescribed herein, may, of course, vary. It is also to be understood thatthe terminology used herein is for the purpose of describing particularembodiments only, and is not intended to limit the scope of the presentinvention.

It must be noted that as used herein and in the appended claims, thesingular forms “a”, “and”, and “the” include plural references unlessthe context clearly dictates otherwise. Thus, for example, reference to“a drug formulation” includes a plurality of such formulations andreference to “a drug delivery device” includes systems comprising drugformulations and devices for containment, storage and delivery of suchformulations.

Unless defined otherwise, all technical and scientific terms used hereinhave the same meaning as commonly understood to one of ordinary skill inthe art to which this invention belongs. Although any methods, devicesand materials similar or equivalent to those described herein can beused in the practice or testing of the invention, the preferred methods,devices and materials are now described.

All publications mentioned herein are incorporated herein by referencefor the purpose of describing and disclosing the compositions andmethodologies which are described in the publications which might beused in connection with the presently described invention. Thepublications discussed herein are provided solely for their disclosureprior to the filing date of the present application. Nothing herein isto be construed as an admission that the invention is not entitled toantedate such a disclosure by virtue of prior invention.

Definitions

The term “controlled substance” as used herein is used with reference todrugs, the prescription and administration of which is highly regulated.In general, “controlled substances” are listed in Schedules I through Vin the United States. Schedule I drugs are not often used medically andSchedule V drugs have a very low risk of abuse, therefore the drugs mosthighly in need of controlled access are included in Schedules II, IIIand IV. Outside the United States (i.e. in Canada, Europe and Japan),the term “controlled substance” is used with reference to any drug thatis legally regulated by the government based on risk of misuse and/orabuse.

The term “formulation” or “drug formulation” or “dosage form” as usedherein refers to a physical entity containing at least one therapeuticagent, i.e., a controlled substance, meant for delivery to a subject. Itmay be in the form of a lozenge, pill, capsule, gel cap, membrane,strip, liquid, patch, film, gel, spray or other form.

The term “drug” as used herein is generally meant to refer to anysubstance that alters the physiology of an animal.

The term “drug” may be used interchangeably herein with the term“therapeutic agent” or “medication”. It will be understood that a “drug”formulation of the invention may include more than one therapeuticagent, wherein exemplary combinations of therapeutic agents include acombination of two or more compounds, wherein one or more of thecombined compounds may be a controlled substance. The term “congener” asused herein refers to one of many variants or configurations of a commonchemical structure.

The term “subject” is includes any subject, generally a mammal (e.g.,human, canine, feline, equine, bovine, ungulate etc.), in whichtreatment for a disorder, such as management of pain or anxiety, isdesired.

The term “drug delivery route”, as used herein refers to any means fordelivering a drug to a patient. Exemplary routes include, but are notlimited to, subcutaneous, intramuscular, intravenous, transdermal,transmucosal, oral (i.e. via the GI tract), intrathecal and epidural.

The term “transmucosal” delivery of a drug and the like is meant toencompass all forms of delivery across or through a mucous membrane.Examples of “transmucosal” delivery include, but are not limited todelivery via the oral, nasal, buccal, ocular, vaginal, and rectalmucosa. In particular, “oral transmucosal” delivery of a drug includesdelivery across any tissue of the mouth, pharynx, larynx, trachea, upperrespiratory tract or upper gastrointestinal tract, particularlyincluding the sublingual, gingival and palatal mucosal tissues.

The term “therapeutically effective amount” means an amount of atherapeutic agent, or a rate of delivery of a therapeutic agent (e.g.,amount over time), effective to facilitate a desired therapeutic effect,such as pain relief. The precise desired therapeutic effect (e.g., thedegree of pain relief, and source of the pain relieved, etc.) will varyaccording to the condition to be treated, the tolerance of the subject,the drug and/or drug formulation to be administered, e.g., the potencyof the therapeutic agent (drug), the concentration of drug in theformulation, and the like, and a variety of other factors that areappreciated by those of ordinary skill in the art. In one exemplaryembodiment, the systems and methods of the invention find utility in thesuppression or mitigation of pain in a subject suffering from pain thatmay be associated with any of a variety of identifiable orunidentifiable etiologies.

The term “treatment” or “management” of pain is used herein to generallydescribe regression, suppression, or mitigation of pain so as to makethe subject more comfortable as determined by subjective criteria,objective criteria, or both.

The term “qualified medical staff” or “qualified medical personnel” asused herein refers to a person who has been authorized to have access tocomputer network of the controlled substance administration andmonitoring system of the invention. Persons who are authorized to haveaccess to computer network must undergo training for use of the systemand HIPAA compliance. Once trained, system users are given a user IDbefore they are given password protected access to the database andbecome a “registered user” or “authorized user”. The user ID links theauthorized person to the prescribing physician and is used to track allactivities by the user relative to the controlled substanceadministration and monitoring system of the invention.

“Device for containing and delivering a controlled substance dosage form” or “drug delivery device” and the like are used herein to refer to anydevice adapted for storage and/or delivery of a controlled substanceformulation such as a nanotab, pill, tablet, lozenge, gel, liquid,strip, film, spray, mist and the like.

“Operatively connected” as used herein means the components are providedin a device so as to function as intended to achieve an aim. Forexample, a memory device operatively connected to a CPU which is furtheroperatively connected to a release mechanism or sensor may be meant toindicate that, upon actuation, the CPU communicates with the memorydevice to check the status or history of drug delivery, and then furthercommunicates with the release mechanism (e.g., via a solenoid and aswitch) to release and deliver a drug.

The term “network” as used herein typically refers to computer networkthat spans a large geographical area. Typically, a WAN consists of twoor more local-area networks (LANs). Computers connected to a wide-areanetwork are often connected through public networks, such as thetelephone system. They can also be connected through leased lines orsatellites. The largest WAN in existence today is the Internet. The term“wired network” as used herein refers to a network that relies oncommunication via a wired system or network such as the telephone orcable system.

The term “wireless network” as used herein refers to communication via asystem or network, without the need for a wired connection. A wirelessnetwork may consist of, but is not limited to, the following wirelesstechnologies: wireless telephone, radio frequency, infra red, laser,optical light, or specific wireless communication protocols such asBluetooth, 802.11, or any other wireless communication protocol.

“Radio Frequency Identification (RFID)” refers to an automaticidentification method, which relies on storing and remotely retrievingdata using devices called RFID tags or transponders. An RFID tag is asmall object that can be attached to or incorporated into a product,animal, or person. RFID tags contain silicon chips and antennas toenable them to receive and respond to radio-frequency queries from anRFID transceiver.

“Sustained drug delivery” refers to release or administration of drugfrom a source (e.g., a drug formulation) over a protracted period oftime, for example, over a period of a minute or more. Sustained drugdelivery is in effect the opposite of bolus drug delivery.

The term “active agent” is used herein to refer to any therapeuticallyactive agent.

The term “drug delivery device” means a device that delivers controlledsubstance dosage forms, which carry a dose of medication to the patient.The controlled substance dosage form delivery device is useful forcontrolled and safe delivery of the drug.

The term “system that includes a controlled substance dosage form anddelivery device” as used herein refers to a system for delivery of acontrolled substance dosage form and control and monitoring of bothefficacious, as well as maximum and minimum doses such that the amountof controlled substance (drug) delivered and the corresponding efficacyand safety are enhanced over currently available systems.

The term “opioid tolerant patient” as used herein means a physiologicalstate characterized by a decrease in the effects of an opioid substance(e.g., analgesia, nausea or sedation) with chronic administration. Anopioid substance is a drug, hormone, or other chemical substance thathas analgesic, sedative and/or narcotic effects similar to thosecontaining opium or its derivatives. If analgesic tolerance develops,the dose of opioid substance is increased to result in the same level ofanalgesia. This tolerance may not extend to side effects and sideeffects may not be well tolerated as the dose is increased.

The term “opioid naive patient” is used herein with reference to apatient who has not received repeated administration of an opioidsubstance over a period of weeks to months.

The term “acute pain” is used herein with reference to pain that istypically present for less than one month, however, in some cases painthat is present for as long as three months may also be considered to be“acute”.

The term “chronic pain” is used herein with reference to pain that istypically present for longer than one month.

GENERAL FEATURES OF THE INVENTION

The present invention encompasses systems and methods for theadministration and monitoring of a controlled substance which iseffected and monitored using a drug delivery device, a means for thedevice to communicate with a computer network station or wirelesscommunication protocol, e.g., by way of a docking station, acommunication component for monitoring the physical state of the patientby measurement of one or more biological parameters, and transmittingdrug delivery information and the biological parameter(s) of the patientto a network such that an alert is sent to qualified medical personnelif there is a problem (e.g., drug dosing outside of prescribed limits)and the drug dose is adjusted as needed. An “alert” may be manuallygenerated or may be automatically generated by the software of thecomputer system of the system of the invention. In either case, an alertcauses an email, text message, page, phone call or other communicationto be sent to the system user who entered the information into thedatabase relative to the relevant prescription or controlled substanceuser and to the prescribing physician.

The present invention is directed to a system for delivery andmonitoring delivery of controlled substance(s), wherein the systemincludes a National Database of controlled substance users, i.e.,AcelRx™ device users. A delivery device, e.g., an AcelRx™ device is usedto administer a controlled substance or drug to a patient, as describedfor example in U.S. Application Ser. No. 60/756,937, expresslyincorporated by reference herein in its entirety.

In using the system of the invention, the prescribing physician or aperson authorized by the prescribing physician (referred to herein as an“authorized user” or “registered user”) will log into the computernetwork and enter the prescription information into a National Databaseof controlled substance users. The prescription information will includethe patient's name, age, address, phone number, emergency contact,social security number or other unique identifier. Regarding the drug,the name, dose and quantity of dosage units of the controlled substance,and the name of the prescribing physician is entered. When a pharmacistreceives a prescription for a controlled substance or drug, that isrequested to be prescribed with a controlled substance delivery devicesuch as an AcelRx™ delivery device, the pharmacy staff will verify thatthe drug being given to the patient matches the “initial NationalDatabase information” which includes the patient's name and otheridentifying information, as well as the drug name, quantity andprescribed dosage which is verified relative to the information in theNational Database. The pharmacy staff will then enter the pharmacyinformation, such as the name of the pharmacy, address, pharmacistsname, drug expiration date and the pill count if different from theprescribed amount. This is important because often pharmacies don't haveenough controlled drugs in stock to completely fill a prescription andinformation relative to dispensing of a partial prescription istherefore entered into the database. The “prescribing information” asdescribed above will be entered into the computer system by a personauthorized by the prescribing physician (i.e., a “registered user”) andverified by the person dispensing the medication every time theprescription is refilled. Any changes in patient identifiers will beupdated in the computer by authorized staff at the prescribingphysician's office (i.e., a “registered user”). Drug delivery devicessuch as an AcelRx™ devices is docked at the pharmacy prior to dispensingin order to have the prescribing information downloaded into the device.In addition to the drug information listed above, lock-out times anddocking times prescribed by the physicians are also downloaded into thedevice software.

Data may be entered into the information network using at least oneinput device, for example, a microphone, a touch screen, a keyboard, ora graphical input device.

The system of the present invention for delivery and monitoring ofcontrolled substance(s), comprises software, i.e., AcelRx™ softwarewhich provides a number of features. One such feature is that additionof a patient name or other identifier to the National Database, triggersthe software to automatically conduct a search to see if the samepatient is receiving scheduled drugs from another prescriber/pharmacy.The search is conducted on a national level. The system will generate analert based on a number of parameters. For example, if a controlledsubstance has been prescribed for the same patient name, same address orsame unique identifier at more than one location, an alert will beissued. If the pharmacist enters drug information that does not matchthe entered prescribing information from the physician's office, analert will be issued. Current systems that track users of controlledsubstances are state specific or pharmacy-chain specific and are delayedregarding feedback and have no direct alerts for prescribing anddispensing mismatches. Also, such systems do not allow for a nationwidetracking of the use of controlled substance. The system of the inventionprovides a mechanism to track abuse, which is not available usingcurrent systems.

In the system of the invention, each dispensing pharmacy also has accessto the information network of the system as well as the appropriatesoftware, i.e., AcelRx™ software, such that they are able to search theNational Database to confirm that the dispensing information for a givenprescription matches the prescribing information entered by thephysician.

The system does not require a paper prescription since the systemsoftware, i.e., AcelRx™ software can provide a direct link between thephysician and the pharmacy.

The National Database is searchable by registered or authorized usersusing the appropriate software, i.e., AcelRx™ software. The database isHealth Insurance Portability and Accountability Act (HIPAA) compliantand provides appropriately ID coded or encrypted patient identifiers toavoid misuse of information/inappropriate access. Users of thecontrolled substance delivery device and monitoring system of theinvention are provided online training for HIPAA compliance. Dockingsystems are used to download patient information/drug usage to and fromthe controlled substance delivery device. This can be done in anylocation where there is a docking station, for example, at a physician'soffice, at a pharmacy or in the patient's home. In some situations, thedocking station is as simple as a data transmission port, i.e. a USBport. In other situations, the docking station is used to measurebiological parameters of the patient.

In one aspect, the controlled substance delivery and monitoring systemof the invention also includes a “physician” database, which interfacesand can exchange data with the National Database. The Physician Databasealso provides an interface and data exchange with a local dockingsystem. The patient data on the Physician Database may include all ofthe data in the National Database and further includes informationregarding use of a given controlled substance by each patient (referredto herein as “patient usage information”). Patient usage information maybe downloaded/transmitted from the controlled substance delivery deviceinto a database of the system of the invention. The information istypically transmitted from the device to the system by way of a dockingstation and the data transmission takes place by way of a bidirectionalcommunication network which may be wireless or may include a directwired or other connection. Such patient usage information includes butis not limited to, device information, drug usage information, such asthe name of the drug in the device, dosage, total pill count used overvarious time frames, lock-out time. Data on other medications thepatient is taking concurrently with the controlled substance may beentered by the physician or pharmacy staff and processed by the systemsoftware, i.e., AcelRx™ software as well as downloaded to the device.

An “alert” is generated by the system software if a possible drug-druginteraction is detected.

When the device used to deliver the controlled substance is docked, thesystem may also collect additional information that can bedownloaded/transmitted to a database, e.g., the Physician Database ofthe system of the invention.

Such additional information includes, but is not limited to, one or morebiological or physiological parameters such as pain score or otherinformation related to the medical condition for which the controlleddrug was prescribed (e.g. sleep score, anxiety score, mood score, etc)temperature, pulse, blood pressure, respiratory rate, oxygen saturation,blood chemistry and/or bodily fluid chemistry information.

The docking system allows for transmission of drug delivery information.The frequency with which the device is docked and information istransmitted to a database, e.g., the Physician Database and reviewedwill vary and is controlled by the prescribing physician's office. Forexample, the device may be docked and information transmitted to theinformation network at daily, weekly, biweekly, monthly or otherinterval. An alert will occur to both the patient and the physician'soffice if the docking interval exceeds what was requested by thephysician.

When the device is docked there is a bidirectional flow of informationbetween the computer network of the controlled substance monitoring andadministration control system and the drug delivery device. Informationthat is transmitted from the drug delivery device to the computernetwork via a docking station includes, but is not limited to:information on use of the device such as number of dosage unitsdelivered, time interval at which they were delivered, number of dosageunits remaining in the device, and biometric, PIN or other securityaccess information The frequency at which the device must be docked isprogrammed into the system by the physician's office. A dock may bedesigned to measure and transmit biomedical or physiological parameters(e.g. blood oxygen saturation and pulse) and symptom scoring (e.g. pain,anxiety) to the information network.

Information that is transmitted to the drug delivery device and patientdock from the computer network includes: information on allowable use ofthe device such as number of dosage units to be delivered, time intervalat which they can be delivered (lock-out time), frequency of dockingnecessary, frequency of biometric or PIN ID entry by the patient, etc.Safe limits for the biological parameters that provide information onthe physiological status of the patient can be changed as well. Forexample, if a patient is known to have a chronic respiratory conditionand normally has oxygen saturations in the range of 91% then the lowerlimit of the alert range for oxygen saturation (usually 92-93%) may beprogrammed lower than 91% for this patient in the system by thephysician.

As suggested above, a physician may have the ability to directlyreprogram the device such that the new information is transmitted to thedevice via the docking system in the office during a visit or remotelyat the patient's home. Parameters that may be changed include, forexample, the unit dose administration lock-out time, the frequency forbiometric patient confirmation prior to delivering the medication,frequency of docking that is required for the delivery device tocontinue to deliver the controlled substance, as well as otherinformation such as battery life, etc.

Software associated with the information network of the system of theinvention and accessible at a doctor's office monitors incominginformation downloaded/transmitted from the drug delivery device when itis docked. An “alert” is also generated by the system software if ascheduled docking is missed, dosing of the controlled substance is outof the prescribed range, there is evidence that the device has beentampered with or if the device has an empty cartridge, i.e. contains nodosage unit forms (i.e., tablets) of the controlled substance.

Once qualified medical personnel, e.g., in the prescribing physician'soffice, become aware of the “alert”, office staff contact the patient todetermine problem. It follows that the controlled substanceadministration and monitoring system of the present invention is aclosed-loop system.

In one exemplary aspect, the controlled substance drug delivery systemof the invention provides for oral transmucosal delivery of controlledsubstances such as opioids or opioid agonists, for the treatment ofacute or break-through pain.

The drug delivery device of a controlled substance dosage form deliverysystem of the invention has a number of features that provide forimproved safety and ease of use over currently available systemsincluding a security feature that prevents unauthorized access to thestored drugs, a lock-out feature, a dose counting feature, a memorymeans for retaining information about dose delivery, and an interfacefor bidirectional exchange of information with another device such as acomputer.

A given patient may be taking more than one medication, at least one ofwhich is a controlled substance. In one aspect of the invention, such apatient may use two or more controlled substance drug delivery devices,each of which can be docked in a docking station in order to down loaddrug dispensing information for each drug into the computer system suchthat the information is stored in the Physician Database. Alternatively,a single controlled substance drug delivery device may be used todeliver more than one medication.

A device for delivery of a controlled substance in conjunction with thesystem of the invention may be used multiple times or be disposable suchthat it is discarded when all of the medication initially loaded intothe device has been delivered.

A drug delivery device of the controlled substance administration systemof the invention has the capacity to store historical device use/drugdelivery information and communicate such information with anotherdevice or computer such that the data is stored in one or more computerdatabases. For example, such information may be communicated bydownloading stored information to a computer using a physically wiredinterface, such as a USB or any other communication connection.Alternatively, information may be communicated via a wireless system.Such information may include historical use information, for example thenumber of dosages stored and delivered, and the times of delivery.

The device may also comprise a means to confirm that the individualattempting to dispense the controlled substance or drug is the patientfor which the drug was prescribed, i.e., by way of a detection mechanismfor patient identification such as an RFID tag, password, pass code, orbiometric identifier, e.g., such as fingerprint information, opticaliris information (i.e. a retinal scan), voice recognition, facialrecognition (i.e. visual scan image recognition of facial features), orgene or DNA characteristics obtained from a bodily fluid sample. Thisserves to confirm that the correct patient is receiving the controlledsubstance or drug and minimizes the possibility for diversion orinappropriate use of the drug.

The physician may mandate that only the patient is allowed to pick-upthe controlled substance (drug)/device combination in order to initiallyactivate device for the specific patient. The device may be initiallypicked up at a pharmacy or be dispensed at a physician's office. Aphysician may override the requirement for biometric information for useof the device and/or identification may not be required prior toadministration of each dose. A physician will determine the frequency ofpatient identification required.

The device may have colored or other visual, audible, or tactileidentifiers to communicate the dosage contained therein.

The drug delivery device may include a microprocessor (CPU) incommunication with a memory means and a display means that enables thedevice to monitor and control dosing, dose frequency, communication,synchronization, user identification, and schedule, and access to thedoses and to store programmed and historical information.

In another aspect, the device is adapted to track and communicate thetotal number of doses remaining in the device to allow anticipation andscheduling of refilling. The device also may record and track drug usageand communicate this, via a wireless network, electronic docking orother means, such that the information is transmitted via a network andaccessible by qualified medical personnel, who can monitor the patient'sdrug use and adjust the dose as needed.

In some embodiments, the device may be remotely programmed to allowoversight by qualified medical personnel and therefore provides a meansfor management and optimization of the administration of controlledsubstances. The delivery device may include a radio frequencyidentification (RFID) system or other remote operation system thatprovides a unique key for each device that must be proximal to thedevice for operation, so as to prevent accidental or intentionaltampering, abuse, or access to the drug by an unauthorized individual.

The system may be used in such a way as to provide for delivery of anopioid antagonist in conjunction with an opioid and/or an addictioncontrol substance such as buprenorphine, in a configuration thatprevents intentional diversion or tampering.

In many cases, the docking station is in a physician's office or otherlocation, such as a pharmacy. In other cases, the system includes adocking station that is in the patient's home. The docking stationprovides a means for downloading drug delivery information from acontrolled substance delivery device. In one approach, a simple feedbackloop would not require a patient home-docking unit but rather the devicewould be queried during physician visits, e.g., every month. At suchvisits the device, if necessary, could be reprogrammed by the physicianas to lock-out time, frequency of biometric ID checks. Since no dockingsystem is at the patient's house, programming the frequency of dockingand setting of limits of biomedical parameters would not be necessary.In another approach, more complex feedback loop would include thepatient's docking system and would allow real-time reprogramming of thedevice parameters by the physician. For example, if the physicianprescribes a higher-strength tablet, then the physician enters the newinformation into the National Database, then the patient would take thedevice to the pharmacy for the new tablets to be dispensed into thedevice by the pharmacist and the prescription is double-checked with theNational Database to assure that no tampering with the prescription hastaken place. The device is then reprogrammed by docking the device atthe pharmacy and downloading this new prescription data (new pill count,new dosage strength, etc). Therefore, there are various levels ofcomplexity and closed loops depending on the number of docking stationsand communication means implemented.

The docking station may include a power supply and provides a means fortransmission of drug delivery information from a controlled substancedelivery device through the network such that it is recorded in adatabase, e.g., the Physician's Database. The information may betransmitted through a wireless, local area network (LAN) or wide areanetwork (WAN) to the Internet via the docking station. The dockingsystem can link into an information network by way of a computer,removable card (or other media), phone line, wireless or otherconnection.

In this way the controlled substance delivery and monitoring systems ofthe invention enable greater oversight and care management by qualifiedmedical personnel.

Current Systems for Administration of Controlled Substances

Current treatment methods for administration of controlled substancesare used for a variety of disorders, including pain management,treatment of anxiety or insomnia, treatment of attention deficit,treatment of opioid addiction, treatment of steroid imbalances andtreatment of excessive sedation are all examples.

In the U.S., controlled substances are placed into Scheduled drugcategories (I-V). Examples of drugs in these categories include:

Schedule I: heroin, mescaline (drugs not used clinically to treatdiseases).

Schedule II: opioids (e.g. morphine, hydromorphone, oxycodone),stimulants (amphetamines), barbiturates (amobarbital, pentobarbital),methylphenidate.

Schedule III: opioids (e.g. hydrocodone, codeine), barbiturates(butalbital), partial opioid agonists (buprenorphine), marinol,methyltestosterone.

Schedule IV: weak kappa agonist opioids (e.g. pentazocine, butorphanol),stimulants (dexfenfluramine, modafinil), benzodiazepines for sleep andanxiety (alprazolam, clonazepam, diazepam, triazolam), barbiturates(phenobarbital), chlordiaxepoxide.

Outpatient Setting

Any of the above examples of controlled substances may be used in thecontrolled substance delivery system of the invention, also referred toherein as the “AcelRx™ system”, Therefore, it follows that users of thesystem may suffer from a variety of medical disorders for which thesystem finds utility. Treatment of acute and chronic pain with opioidsis described below as one set of examples, but one skilled in the artwill understand that this system may be used to deliver controlled drugsfor treatment of anxiety, insomnia, excessive sedation, hormoneimbalance, opioid-resistant pain (with the use of ketamine for example),nausea or decreased appetite (with the use of Marinol for example),attention deficit disorder or hyperactive disorders, and various otherconditions requiring the use of controlled substances.

Treatment of severe acute and chronic pain is often necessary forpatients in an outpatient setting. For example, many patients sufferfrom chronic pain and require the use of opioids on a weekly or dailybasis to treat their pain. While they may have a long-acting oral ortransdermal opioid preparations to treat their chronic underlying painlevels, they often need short-acting potent opioids to treat theirsevere breakthrough pain levels.

Acute and chronic pain also needs to be treated in patients who may havea history of drug abuse and the physician is afraid of prescribingopioids on an outpatient basis. Data from the Drug Abuse Warning Network(DAWN) from 1990-1996 indicate that the abuse of opioid analgesicsaccounts for 3.8-5.1% of emergency department presentations, yetwithholding pain relief to patients with a history of drug abuse is nota viable solution.

In the above clinical settings, there is clearly a need for a system foradministration and monitoring of controlled substances which providesfor improved safety and efficacy.

Controlled substances may be administered by any of a number of routesincluding oral, transmucosal (i.e. sublingual, intranasal, buccal,rectal, vaginal), subcutaneous injection, intramuscular injection,transdermal, epidural and intrathecal. Therefore the drug deliverydevice may be constructed in any of a variety of ways that enabledelivery of the various forms in which medications comprising controlledsubstances are administered. For example, the drug delivery device willvary such that it is able to deliver any of a number of dosage forms,including, but not limited to: pills, sublingual lozenges, patches,suppositories, injectable syringes, sprays, gels, liquids, etc. It willbe understood that the delivery route and configuration of the drugdelivery device will not affect the bidirectional communication,monitoring and control aspects of the system of the invention.

The oral route of administration is the most widely used route and mostacceptable for the patient. Disadvantages of the oral route is thatabsorption of drugs may be reduced by the delay in gastric uptake, aswell as nausea and vomiting. Thus the oral route may be unsuitable insome instances.

The sublingual route offers some theoretical advantages for drugadministration. Absorption occurs directly into the systemic circulationas there is no first pass metabolism. This is also true for theintranasal and buccal routes. Rectal or vaginal administration provideuseful transmucosal alternatives.

Subcutaneous injection and intramuscular injection represent anothertechnique for delivery of drugs, however this requires invasive accessand produces discomfort for the patient and therefore is not highlydesirable.

Intravenous administration has been routinely used in the in patientsetting, but is rarely used on an outpatient basis due to difficulty inobtain intravenous access and also because opioids, for example, areinherently dangerous if the patient is left unsupervised for even ashort period.

Examples of Use of Controlled Substances

Use of Opioids

Opioids are powerful analgesics and are utilized to treat both acute andchronic pain of moderate to severe intensity throughout the world.However, they can also have severe respiratory depressive effects if notused appropriately and suffer from a high abuse potential. In 1998, atotal of 36,848 opiate exposures (pure and mixed preparations) werereported to US poison control centers, of which 1227 (3.3%) resulted inmajor toxicity and 161 (0.4%) resulted in death. The predominant causeof morbidity and mortality from pure opioid overdoses is via respiratorycomplications.

Opioids are still widely used for the treatment of pain, and aregenerally delivered via numerous routes of administration, including butnot limited to intravenously, orally, transmucosally, epidurally,intrathecally, transdermally, subcutaneously and intramuscularly.Opioids exert their actions via the mu opioid receptor, which is locatedon peripheral nerve terminals, both pre- and post-synaptically in thespinal cord, brainstem, mid-brain and cortical regions associated withsensory and pain processing.

Opioids are known to produce physical dependence, possible addictivebehaviors and tolerance with long-term use. In one aspect of theinvention, the administration of a controlled substance is effected andmonitored using the controlled substance drug delivery system of theinvention wherein the controlled substance includes an opioid agonist.There are many types of opioids, including mu-opioid receptor agonistssuch as endogenous agonists, e.g. beta-endorphin; endomorphins; smallpeptide agonists, e.g. DAMGO (D-Ala, N-Me-Phe, Gly-ol)-enkephalin orDALDA (H-Dmt-D-Arg-Phe-Lys-NH2); non-peptide agonists, such as morphine,hydromorphone, buprenorphine, oxycodone, tramadol, etorphine,levorphanol, etonitazene and analogues, tilidine and analogues, e.g. theactive metabolite nortilidine, loperamide and piritramide; delta-opioidreceptor agonists, such as: endogenous agonists, e.g. met-enkephalin(Tyr-Gly-Gly-Phe-Met) and leu-enkephalin (Tyr-Gly-Gly-Phe-Leu); smallpeptides, e.g. DADLE (D-Ala 2, D-Leu 5) enkephalin or DPDPE(tyrosyl-2,6-3H(N)-(2-D-penicillamine-5-D-penicillamine)-enkephalin);non-peptide agonists, such as BW373U86(±)-4-(a-R)-a(2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-hydroxybenzyl)-N, N-diethylbenzamide or SNC80(±)-4-(a-R)-a(2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl)-N, N-diethylbenzamide; kappa-opioid receptor agonists, such as:endogenous agonists, e.g. dynorphin A arylacetamides, e.g. spiradoline(U62, 066), U69,593([5alpha,7alpha,8beta]-N-methyl-N-[7-[1-pyrrolidinyl]-1-oxaspiro[4.5]dec8-yl]-benzenacetamide),U50,488, benzomorphans, e.g. cyclazocine, bremazocine, pentazocine,Nalfurafine, salvinorin A; and ORL-A1 receptor agonists, such as:endogenous agonists, e.g. nociceptin; small peptides, e.g. Ro 64-6198((1S,3aS)-8-(2,3,3a, 4,5,6-hexahydro-1H-phenalen-1-yl)-1-phenyl-1,3,8-triaza- spiro[4.5]decan-4-one).

In one aspect of the invention, the administration of a controlledsubstance is effected and monitored using the controlled substance drugdelivery system of the invention and the controlled substance includes acombination of two or more opioid analogues, such as sufentanil plus anopioid such as fentanyl, alfentanil, or remifentanil, or opium alkaloidssuch as morphine and codeine; semi-synthetic opioids such as heroin andoxycodone; and fully synthetic opioids such as pethidine and methadone,that have structures unrelated to the opium alkaloids.

In alternative embodiments, the controlled substance drug deliverysystem of the invention is used to deliver at least one opioid drug andone or more other drugs wherein the other drug may be an opioid ornon-opioid drug. The non-opioid drug may be added to increase analgesicefficacy or to help deter abuse or to avoid opioid-induced side effects.

Examples of the classes of drugs which could be added to the opioid toincrease analgesic efficacy may include but are not limited to:anti-inflammatory drugs, such as non-steroidal anti-inflammatory drugs(including cyclooxygenase inhibitors and lipoxygenase inhibitors),steroid anti-inflammatory drugs, acetaminophen, cytokine antagonists,tumor necrosis factor antagonists, prostaglandin receptor antagonists.Also included are drugs that are analgesic via non-anti-inflammatorymechanisms, such as sodium channel blockers, N-type calcium channelblockers, monoamine uptake inhibitors, n-methyl-d-aspartate receptorantagonists, gamma aminobutyric acid (GABA)-A or GABA-B receptoragonists, or other receptor agonists or antagonists or enzyme inhibitorsknown by one skilled in the art to be of analgesic benefit.

Examples of drugs added to avoid abuse may include but are not limitedto naloxone and naltrexone or other opioid receptor antagonists.Examples of drugs added to reduce opioid-induced side effects mayinclude but are not limited to: anti-pruretic drugs, such asanti-histamines, anti-constipation drugs or gut stimulants, such asmetoclopramide, anti-sedation drugs, such as stimulants, (e.g.modafinil) and anti-emetic drugs, such as meclizine or dimenhydrinate.

Opioid antagonists include mu-opioid receptor antagonists such asnaltrexone; naloxone; peptide antagonists, e.g.D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr amide beta-funaltrexamine;delta-opioid receptor antagonist such as naltriben and naltrindol;kappa-opioid receptor antagonists such as nor-binaltorphimine and5′-acetamidinoethylnaltrindole; and ORL-1 receptor antagonists such asPhe1 {Psi} (CH2-NH) Gly2] nociceptin (1-13) NH2 and SB-612111((-)-cis-1-Methyl-7-[[4-(2,6-dichlorophenyl)piperidin-1-yl]methyl]-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-ol).

SUBOXONE® delivers transmucosal buprenorphine with naloxone fortreatment of addiction. The controlled substance drug delivery system ofthe invention finds utility in delivery of this drug because patientsbeing treated for addiction would greatly benefit from regulated accessto this partial agonist opioid medication and would be able to reducethe number of visits to the addiction specialist's office per month.

Those of skill in the art will appreciate that the drug delivery systemsof the current invention provide advantages over current methods bycontrolling the administration of controlled substances and monitoringthe delivery process such that the dose can be optimized for efficacywhile reducing side effects and potential for abuse.

Opioids remain the most powerful form of analgesics, however, improvedforms are needed, that have minimal side effects, and can be deliveredto patients in a manner in which patient use can be easily tracked bythe physician.

The present invention provides a mean for insuring that the correctpatient receives the medication, that potential drug-drug interactionsare detected, that the prescribed dose is adjusted as needed, and thatthe delivery process is monitored in a manner effective to maximizeefficacy while reducing side effects and minimizing the potential forabuse.

There is a continuing, unfilled need for a system for administration ofcontrolled substances that includes a drug delivery device that canaccurately deliver a given medication to the correct patient in a mannerthat is cost-effective, minimizes the risk of error, is resistant topilferage, is not labor-intensive and minimizes the possibility forabuse. The drug delivery device of the controlled substanceadministration system of the present invention is easily handled,portable, relatively inexpensive and allows for lock-out to avoidoverdosing, is child-proof and has theft-proof safety features. Inaddition, the system provides for multi-unit dosing, such that days,weeks or more of a given medication can be housed in a single device.The present invention meets that need.

Exemplary Uses of the Controlled Substance Administration and MonitoringSystem of the Invention Include the Following

1. Out-patient treatment of a post-operative patient after surgery totreat acute pain (e.g. opioids).

2. Out-patient treatment of a patient with chronic pain.

3. Out-patient treatment of a patient suffering from severe chronic painof malignant or non-malignant origin who also has episodes of severebreakthrough pain.

4. Treatment and monitoring of a patient with a known or suspectedhistory of substance abuse who presents with severe pain.

5. Treatment and monitoring of a patient requiring controlled drugs totreat anxiety (e.g., benzodiaxepines).

6. Treatment and monitoring of a patient requiring controlled drugs totreat insomnia (e.g. benzodiazepines).

7. Treatment and monitoring of a patient requiring controlled drugs totreat attention deficit/hyperactive disorder (e.g., methylphenidate).

8. Treatment and monitoring of a patient requiring controlled drugs totreat excessive sedation (amphetamines, modafinil).

9. The ability to track controlled substance misuse or abuse by a givenpatient and detect abuse based on the filling of the same or similarprescriptions at multiple pharmacies.

10. The ability to avoid patient tampering of prescription betweenphysician's office and pharmacy by having a electronic National Databasewith which to compare the written prescription or to have a directelectronic download of the prescription from the physician's office tothe pharmacy.

11. The ability to deter attempts by persons other than the patient toself-administer the controlled substance through the use of biometric orother security systems.

12. The ability to avoid accidental misuse of a controlled medicationdue to unclear instructions or patient forgetfulness by providing a drugdelivery device with an electronic lock-out timer and a patient reminderalert.

13. The ability to regulate dosing frequency remotely based on apatient's parameters, such as pain score, by using the docking system toreprogram the device lock-out time as instructed by the physician'soffice.

14. The ability to gather dosing information on a pre-set frequency bysetting a required docking frequency on the device to alert thephysician's office if the patient is either purposefully not docking thedevice to avoid abuse detection or is not able to dock the device due toa medical emergency, such as a heart attack, stroke or other injury.

15. Electronic and printable graphs of drug dosing over any given timeframe to allow the patient chart in a physician office to contain thisdata.

16. The ability to wean a patient off a drug in a controlled manner byprogressively programming the lock-out period for longer time intervalsbetween dosing. This would be used for any drug which promotes physicaldependence on the drug and requires a slow, methodical wean to avoid anacute withdrawal reaction.

The present invention is described by reference to the followingexamples, which are offered by way of illustration and are not intendedto limit the invention in any manner. Standard techniques well known inthe art or the techniques specifically described below are utilized.Therefore, the description and examples should not be construed aslimiting the scope of the invention, which is delineated by the appendeddescription of exemplary embodiments.

EXAMPLES

For purposes of illustration a few exemplary systems and scenarios fortheir use are provided below:

Example 1 Exemplary Outpatient System for Delivery and Monitoring ofAdministration of Controlled Substances

A patient is a 46 year-old man who suffers from severe low back painafter three back surgeries. He has a distant history of alcohol abuseand methamphetamine abuse. His pain physician would like to start him onmorphine sulfate extended release pills prescribed in a controlledsubstance delivery device. The prescription is written for 30 mgtablets, one every 8 hours, dispense 90 tablets for a 30-day supply. Thelock-out time is set for 8 hours and the device docking frequency isentered as every 24 hours since the patient has a history of drug andalcohol abuse. The physician's nurse enters the patient's identifyinginformation in the National Database of the information network alongwith the prescription as written by the physician and checks to see ifthe patient is receiving any other controlled drug that is recorded inthe system. The patient brings the prescription to the pharmacy in hishome town. The pharmacist notes that the drug is to be delivered with acontrolled substance delivery device such as an AcelRx™ device so sheenters the National Database and checks to see that the writtenprescription is the same as the entered data from the physician'soffice. She fills the proper device with 90 tablets of morphine sulfateER and docks the device so that the patient identifiers and prescribeddrug and dosing parameters (drug, pill number, dosing frequency, dockingfrequency, etc) can be downloaded to the device. The pharmacist thenasks the patient for photo identification and asks the patient toactivate the biometric fingerprint pad, or other form of securitytracking, such as personal identification number (PIN). The patientpurchases a docking station and at this time the device is ready forhome use. The patient goes home and when the patient desires toself-administer a dose of the morphine for pain relief using the systemof the present invention, he holds the delivery device, and pushes anybutton to wake the device up from its sleep mode. The device will querythe user for a thumbprint reading, PIN or some other means ofidentification. The patent will be required to provide the identifyinginformation once per day as a default (or on a frequency that can beprogrammed by the physician). The device queries its internal memory andclock to make sure that the dosage regimen programmed into the device isnot being violated by the current usage request. The device thendelivers a tablet. Attempts to obtain a tablet before the lock-out timeof 8 hours are captured electronically. The patient becomes agitated atwaiting 8 hours to take another morphine tablet. He attempts multipletimes to delivery another tablet before the 8 hour lock-out time. Hethen gets frustrated and goes to another pain physician in a nearby townto try to obtain a prescription for Vicodin. This physician also usesthe controlled substance administration and monitoring system of theinvention and logs into the National Database and sees that the patientjust received morphine from a pain physician in another town and entersa few sentences describing the encounter. The National Database recordsthe query by the second doctor even though no drug was prescribed andsends an alert email to the first physician's office. When the patientreturns to the first pain physician's office, the device is docked on adocking station and the patient usage information is downloaded into thecomputer system of the controlled substance administration andmonitoring system of the current invention. A graph of the patient'sdrug usage and attempts shows that the patient tried numerous times todeliver a tablet before the 8 hour lock-out time. Also, the nurses atthe office had alerted the physician to the query and message from thesecond physician. The pain physician confronts the patient with thisdata and suggests that non-opioid pain treatments will be used since thepatient is too high-risk to use opioids reliably. If the physician hadnot used the controlled substance administration and monitoring systemof the current invention, the first physician would not be aware of themisuse of the morphine tablets and the second physician would haveprescribed the Vicodin to the patient not knowing that he had justreceived morphine tablets from another physician. The patient would haveused a different pharmacy so even the pharmacy staff would not be awareof the multiple prescriptions for opioids.

Example 2

The patient is a 78 year-old woman with metastatic breast cancer livingalone. She does not want to be admitted to hospice. She is quiteforgetful and is suffering with severe pain and shortness of breath frommetastatic lesions to her ribs and lungs. Her physician prescribes heroxycodone immediate release for severe breakthrough pain. The dose is 10mg with a lock-out every 3 hours. The physician is not sure of thepatient's mental status and understanding of her directions on how totake the medication. The physician is not concerned about purposefulabuse, so she prescribes a docking frequency of every 12 hours but nobiometric or PIN ID frequency. The patient brings the prescription tothe pharmacy and they tell her how to plug in the docking station to hertelephone line and that the device needs to be placed on the dock every12 hours or it will alarm. She also puts her finger on the dockingstation to record pulse and oxygen saturation every 12 hours when shedocks the device. One week later there is an alert to the physician'soffice that the oxygen saturation in this patient is low. The nursecalls the patient at home and the patient sounds quite sedated on thephone and tells the nurse that she has no pain but has been taking theoxycodone every 3 hours because she is afraid of dying in pain. Thenurse explains that this frequency may be too often and that it iscausing her to have too low of an oxygen level in her blood. She tellsthe patient to dock the device so that remotely it can be reprogrammedfor a lock-out of every 6 hours instead of every 3 hours. The patienthas home nasal cannula oxygen for use on an as needed basis and thenurse recommends that she use it for the next 12 hours. Her next dockingtime shows that her oxygen levels are back to normal.

Without the controlled substance administration and monitoring system ofthe invention, the patient would have continued to take the opioidtablets every 3 hours because of a misunderstanding, resulting inhypoxia and possibly a cardiac arrest. Since no one is living at homewith her it could have been days before this was discovered.

Example 3

A 24 year-old girl has attention deficit disorder and usesmethylphenidate which her physician prescribes using a drug deliverydevice and the controlled substance administration and monitoring systemof the invention. The patient calls the office and leaves a message thatshe is about to run out of drug early because the pharmacy didn't giveher enough but fails to leave any information as to what pharmacy sheused to fill the prescription. It is a weekend and the doctor calls thepatient back but only gets her voicemail. He logs into the AcelRx™system and finds the name and pharmacy where the drug was dispensed andsees that only a partial fill of the prescription (75 instead of 90tablets) was given to the patient due to low drug supply ofmethylphenidate at that pharmacy. The doctor is leaving town the nextday but writes another prescription early and leaves it with the officefront desk for the patient to pick-up Monday morning.

Without the system of the invention, the doctor would have wasted timetrying to contact the patient for the pharmacy information and then tryto contact the pharmacy to verify that a partial prescription fill wasindeed performed. Since the physician was leaving town, this may or maynot have happened in time for the patient to have received a newprescription. This is a Schedule II drug in the U.S. and therefore itcan not be called into the pharmacy over the phone. A doctor's writtenprescription is needed.

Example 4

A 53 year-old man has a history of Vicodin addiction and is under thecare of a physician who is an addiction specialist. The specialist hasswitched the patient from Vicodin to buprenorphine/naloxone sublingually(Suboxone) in order to begin a slow taper. The patient has very littleself-control and the doctor finds himself having to see the patientevery other day to prescribe small quantities of pills or the patientwill take all the medication at once and run out days or weeks too earlyand be in massive withdrawal. Instead the physician decides to use thecontrolled substance administration and monitoring system of theinvention to provide controlled delivery of the medication. He can nowwrite a prescription for a full month of medication, 2 mg tabletsstarting with 8 tablets per day the first week, followed by a taper ofone tablet every week for a total of 8 weeks. The patient will dock thedevice every day so that the physician can check on his usage and once aweek the physician will download a new pill number to be delivered perday to continue the weaning process. After the first month, the patientwill return to the physician's office for the last month supply and agraph of the first month usage will be placed in the patient's chart.

Without the system of the invention, the patient and the physician wouldhave to have met every few days for two months with a huge cost in timeand money to the health care system and/or the patient. Also the patientwould not be able to travel or go out of town for two months.

Although the foregoing invention has been described in some detail byway of illustration and example for purposes of clarity andunderstanding, it will be apparent to those skilled in the art thatcertain changes and modifications may be practiced. Various aspects ofthe invention have been achieved by a series of experiments, some ofwhich are described by way of the following non-limiting examples.Therefore, the description and examples should not be construed aslimiting the scope of the invention, which is delineated by the appendeddescription of exemplary embodiments.

1. A computer aided system for delivery and monitoring delivery of acontrolled substance to a patient, comprising: (a) an informationnetwork comprising a computing platform and software comprising a searchmechanism running on said computing platform; (b) at least oneinformation storage device connectable to said computing platform forstoring said software; (c) one or more databases for storing patientusage information and prescription information for at least onecontrolled substance; (d) at least one device for administering acontrolled substance to a patient connectable to said informationnetwork for transmission of patient usage information to saidinformation network; and (e) a communications interface for establishinga bidirectional communication link to at least one external source. 2.The system according to claim 1, wherein said prescription informationcomprises information regarding said patient and is stored in a nationaldatabase of controlled substance users.
 3. The system according to claim2, wherein said national database of controlled substance users is incompliance with Health Insurance Portability and Accountability Act(HIPAA) regulations.
 4. The system according to claim 2, wherein saidnational database of controlled substance users provides coded orencrypted patient information to avoid misuse of information orinappropriate access.
 5. The system according to claim 2, wherein saidprescription information for at least one controlled substance comprisesa prescription for a controlled substance issued by a prescribingphysician and said prescription information is entered into saidinformation network by a registered user.
 6. The system according toclaim 1, wherein said system further comprises a software generatedalert when a search of said national database indicates thatprescription information for more than one controlled substance has beenentered into said national database for the same patient during the sametime period.
 7. The system according to claim 6, wherein said softwaregenerated alert is transmitted to said prescribing physician and saidregistered user.
 8. The system according to claim 1, wherein said systemfurther comprises a software generated alert when a search of saidnational database indicates the possibility of a drug-drug interactionand said alert is transmitted to said prescribing physician and saidregistered user.
 9. The system according to claim 1 wherein said atleast one device is connected to said information network by way of adocking station and patient usage information is transmitted to saidinformation network and stored in at least one database.
 10. The systemaccording to claim 1, wherein said docking station is connected to theinformation network by way of connection selected from the groupconsisting of a computer, removable card (or other media), a phone line,a wireless connection and a USB port.
 11. The system according to claim9, wherein said at least one device for administering a controlledsubstance comprises a detection mechanism for patient identification.12. The system according to claim 11, wherein said detection mechanismfor patient identification is a biometric indicator selected from thegroup consisting of an RFID tag, a password, a pass code, fingerprintinformation, optical information, voice recognition, facial recognitionand DNA analysis of a bodily fluid sample.
 13. The system according toclaim 1, further comprising at least one input device for manuallyentering information into said system for delivery and monitoringdelivery of controlled substances.
 14. The system according to claim 13,wherein said at least one input device is a microphone, a touch screen,a keyboard, or a graphical input device.
 15. The system according toclaim 5, wherein said prescribed controlled substance is loaded intosaid at least one device at a physician's office.
 16. The systemaccording to claim 5, wherein said prescribed controlled substance isloaded into said at least one device at a pharmacy.
 17. The systemaccording to claim 1, further comprising a visual display device fordisplaying patient usage information.
 18. The system according to claim1, wherein information is transmitted to, form or within said system bya communication means selected from the group consisting of a telephone,an Internet connection, a WAN network connection, a LAN networkconnection, a wireless connection and a satellite connection.
 19. Thesystem according to claim 1, wherein said at least one database storespatient usage information and said system further comprises at least oneoutput device which outputs said patient usage information stored insaid database.
 20. A method for delivery and monitoring ofadministration of a controlled substance to a patient, comprising,providing a computer aided system for delivery and monitoringadministration of a controlled substance to a patient according to claim1, comprising the steps of: (a) issuance of a prescription for acontrolled substance by a physician; and (b) input of prescriptioninformation regarding said prescription and said patient into said aninformation network via bidirectional communication, wherein said systemsoftware conducts a search of said one or more databases to determine ifmore than one controlled substance prescription issued by a prescribingphysician has been filled for said patient during the same time periodand a system generated alert is issued if said software determines thatmore than one controlled substance prescription has been dispensed forsaid patient during the same time period.
 21. The method according toclaim 20, further comprising a system generated alert, said alerttransmitted to said prescribing physician and said registered user whensaid software determines that more than one controlled substanceprescription has been dispensed for said patient during the same timeperiod.
 22. The method according to claim 21, wherein a system generatedalert is transmitted to said prescribing physician and said registereduser by communication selected from the group consisting of an email, atext message, a page, a phone call or other communication.
 23. Themethod according to claim 22, further comprising input of changes tosaid prescription information for at least one controlled substance intosaid information network by a registered user.
 24. The method accordingto claim 20, further comprising said system software conducting a searchof said one or more databases to determine if dispensing of saidcontrolled substance might result in a drug/drug interaction.
 25. Themethod according to claim 24, wherein a system generated alert istransmitted to said prescribing physician and said registered user whensaid software determines that a drug/drug interaction is possible. 26.The method according to claim 25, wherein a system generated alert istransmitted to said prescribing physician and said registered user bycommunication selected from the group consisting of an email, a textmessage, a page, a phone call or other communication.
 27. The methodaccording to claim 20, further comprising loading of at least onecontrolled substance into said at least one device for administering acontrolled substance and dispensing said loaded device to a patient whenno alert is generated by said system.
 28. The method according to claim27, further comprising verifying said patient identity and activatingsaid drug delivery device once said verification is complete.
 29. Themethod according to claim 28, further comprising self-administration ofsaid controlled substance by said patient with said activated drugdelivery device.
 30. The method according to claim 20, furthercomprising storage of said prescription information and informationregarding said patient in a national database of controlled substanceusers.
 31. The method according to claim 30, wherein said nationaldatabase of controlled substance users is in compliance with HealthInsurance Portability and Accountability Act (HIPAA) regulations. 32.The method according to claim 30, wherein said national database ofcontrolled substance users provides coded or encrypted patientinformation to avoid misuse of information or inappropriate access. 33.The method according to claim 20, further comprising connection of saidat least one device for administering a controlled substance to saidinformation network by way of a docking station, wherein patient usageinformation is transmitted to said information network via said dockingstation.
 34. The method according to claim 33, wherein said dockingstation wherein is connected to the information network by way ofconnection selected from the group consisting of a computer, removablecard (or other media), a phone line, a wireless connection and a USBport.
 35. The method according to claim 20, further comprising storageof said patient usage information in said one or more databases.
 36. Themethod according to claim 27, wherein said at least one device foradministering a controlled substance comprises a detection mechanism forverifying patient identity.
 37. The method according to claim 36,wherein said detection mechanism for verifying patient identity isselected from the group consisting of an RFID tag, a password, a passcode, fingerprint information, optical iris information, voicerecognition, facial recognition and DNA analysis of a bodily fluidsample.
 38. The method according to claim 36, further comprisingverifying patient identity on a daily basis.
 39. The method according toclaim 36, further comprising verifying patient identity on a weeklybasis.
 40. The method according to claim 36, further comprisingverifying patient identity on a monthly basis.
 41. The method accordingto claim 20, further comprising manually entering information into saidsystem for delivery and monitoring delivery of controlled substancesusing at least one input device.
 42. The method according to claim 41,wherein said at least one input device is a microphone, a touch screen,a keyboard or a graphical input device.
 43. The method according toclaim 20, further comprising loading said controlled substance into saidat least one device for administering a controlled substance at aphysician's office.
 44. The method according to claim 20, furthercomprising loading said controlled substance into said at least onedevice for administering a controlled substance at a pharmacy.
 45. Themethod according to claim 20, wherein said system comprises at least onevisual display device, further comprising, displaying on said at leastone visual display patient usage information.
 46. The method accordingto claim 20, further comprising, collecting information on biologicalparameters of said patient by way of said docking station.
 47. Themethod according to claim 46, wherein information on biologicalparameters of said patient is information selected from the groupconsisting of pain score, anxiety score, insomnia score, temperature,pulse, blood pressure, respiratory rate, oxygen saturation, bloodchemistry and bodily fluid chemistry.
 48. The method according to claim33, further comprising: review of said transmitted patient usageinformation to assist qualified health care personnel in verifying oradjusting a controlled substance prescription.
 49. The method accordingto claim 33, further comprising the step of: input of changes to saidcontrolled substance prescription information of the patient by aregistered user wherein said changed prescription information istransmitted to said information network.
 50. The method according toclaim 49, further comprising the step of: docking said at least onedevice for administering a controlled substance wherein said changedprescription information is transmitted to said device.
 51. The methodaccording to claim 49, wherein said input is in response to an alert.52. The method according to claim 49, wherein said input is in responseto information obtained from docking said drug delivery device.
 53. Amethod according to claim 33, wherein information obtained from dockingsaid drug delivery device is displayed visually on at least one visualdisplay device.
 54. The method according to claim 53, wherein saidpatient usage information comprises dosing frequency and number ofdosage unties remaining in the device.
 55. A method according to claim20, wherein information is transmitted to, from or within said system bya communication means selected from the group consisting of a telephone,an Internet connection, a WAN network connection, a LAN networkconnection, a wireless connection and a satellite connection.